Alpha This is a work in progress and may change. Your feedback is very welcome.
  


4HX1

HLA-A*68:02 binding "SVYDFFVWL" at 1.80Å resolution

Data provenance

Structure downloaded from PDB Europe using the Coordinate Server. Aligned to residues 1-180 of 1HHK2 using the CEALIGN3 function of PyMol4. Chain assigment using a Levenshtein distance5 method using data from the PDBe REST API6. Organism data from PDBe REST API. Data for both of these operations from the Molecules endpoint. Structure visualised with 3DMol7.

Information sections


Complex type

Class i with peptide

1. Beta 2 microglobulin
['B']
2. Class I alpha
HLA-A*68:02
['A']
3. Peptide
SVYDFFVWL
['C']

Species


Locus / Allele group


Publication

Structural basis for the differential classification of HLA-A*6802 and HLA-A*6801 into the A2 and A3 supertypes.

Niu L, Cheng H, Zhang S, Tan S, Zhang Y, Qi J, Liu J, Gao GF
Mol. Immunol. (2013) 55, 381-92 [doi:10.1016/j.molimm.2013.03.015]  [pubmed:23566939

High polymorphism is one of the most important features of human leukocyte antigen (HLA) alleles, which were initially classified by serotyping but have recently been re-grouped into supertypes according to their peptide presentation properties. Two relatively prevalent HLA alleles HLA-A*6801 and HLA-A*6802, are classified into the same serotype HLA-A68. However, based on their distinct peptide-binding characteristics, HLA-A*6801 is grouped into A3 supertype, whereas HLA-A*6802 belongs to A2 supertype, similar to HLA-A*0201. Thusfar, the structural basis of the different supertype definitions of these serotyping-identical HLA alleles remains largely unknown. Herein, we determined the structures of HLA-A*6801 and HLA-A*6802 presenting three typical A3 and A2 supertype-restricted peptides, respectively. The binding capabilities of these peptides to HLA-A*6801, HLA-A*6802, and HLA-A*0201 were analyzed. These data indicate that the similar conformations of the residues within the F pocket contribute to close-related peptide binding features of HLA-A*6802 and HLA-A*0201. However, the overall structure and the peptide conformation of HLA-A*6802 are more similar to HLA-A*6801 rather than HLA-A*0201 which illuminates the similar serotype grouping of HLA-A*6802 and HLA-A*6801. Our findings are helpful for understanding the divergent peptide presentation and virus-specific CTL responses impacted by MHC micropolymorphisms and also elucidate the molecular basis of HLA supertype definitions.

Structure deposition and release

Deposited: 2012-11-09
Released: 2013-10-02
Revised: 2013-10-02

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Nonamer (9 amino acids)

Sequence: SVYDFFVWL

Interactive view
Cutaway side view (static)
Surface top view (static - coloured by atom property)
Cutaway top view (static)

Data provenance

MHC:peptide complexes are visualised using PyMol. The peptide is superimposed on a consistent cutaway slice of the MHC binding cleft (displayed as a grey mesh) which best indicates the binding pockets for the P1/P5/PC positions (side view - pockets A, E, F) and for the P2/P3/PC-2 positions (top view - pockets B, C, D). In some cases peptides will use a different pocket for a specific peptide position (atypical anchoring). On some structures the peptide may appear to sterically clash with a pocket. This is an artefact of picking a standardised slice of the cleft and overlaying the peptide.


Peptide neighbours

P1 SER

TYR171
TYR59
TYR7
TYR159
THR163
ARG62
ASN63
TRP167
MET5
P2 VAL

TYR9
ASN66
VAL67
TYR7
MET45
TYR99
TYR159
ASN63
P3 TYR

TYR9
ASN66
TRP156
ARG97
GLN70
TYR99
TYR159
P4 ASP

ASN66
P5 PHE

VAL152
GLN155
TRP156
TYR159
P6 PHE

THR73
ALA69
P7 VAL

VAL152
GLN155
ARG97
TRP147
THR73
ASP77
P8 TRP

VAL76
LYS146
TRP147
THR73
ASP77
P9 LEU

THR143
TYR116
LEU81
TYR123
THR80
LYS146
TRP147
ASP77
TYR84

Colour key

Aromatic Hydrophobic Acidic Basic Neutral/polar

Data provenance

Neighbours are calculated by finding residues with atoms within 5Å of each other using BioPython Neighboursearch module. The list of neighbours is then sorted and filtered to inlcude only neighbours where between the peptide and the MHC Class I alpha chain.

Colours selected to match the YRB scheme. [https://www.frontiersin.org/articles/10.3389/fmolb.2015.00056/full]


Binding cleft pockets


Peptide sidechain binding pockets (static)
Peptide terminii and backbone binding residues (static)
A Pocket

TYR159
THR163
TRP167
TYR171
MET5
TYR59
ASN63
ASN66
TYR7
B Pocket

ALA24
VAL34
MET45
ASN63
ASN66
VAL67
TYR7
GLN70
TYR9
TYR99
C Pocket

GLN70
THR73
ASP74
TYR9
ARG97
D Pocket

HIS114
GLN155
TRP156
TYR159
LEU160
TYR99
E Pocket

HIS114
TRP147
VAL152
TRP156
ARG97
F Pocket

TYR116
TYR123
THR143
LYS146
TRP147
ASP77
THR80
LEU81
TYR84
ILE95

Colour key

Binds N-terminus Binds P1 backbone Binds P2 backbone Binds PC-1 backbone Binds C-terminus

Data provenance

N-/C-terminus and peptide backbone binding residues are assigned according to previously published information and pockets are assigned according to an adaptation of a previously published set of residues. All numbering is currently that of the 'canonical' structures of human and mouse MHC Class I molecules.

Chain sequences

1. Beta 2 microglobulin
Beta 2 microglobulin
        10        20        30        40        50        60
IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDW
        70        80        90
SFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM

2. Class I alpha
HLA-A*68:02
IPD-IMGT/HLA
[ipd-imgt:HLA34809]
        10        20        30        40        50        60
GSHSMRYFYTSMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW
        70        80        90       100       110       120
DRNTRNVKAQSQTDRVDLGTLRGYYNQSEAGSHTIQRMYGCDVGPDGRFLRGYHQYAYDG
       130       140       150       160       170       180
KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQWRAYLEGTCVEWLRRYLENGKETLQ
       190       200       210       220       230       240
RTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT
       250       260       270
FQKWVAVVVPSGQEQRYTCHVQHEGLPKPLTLKW

3. Peptide
SVYDFFVWL


Data provenance

Sequences are retrieved via the Uniprot method of the RSCB REST API. Sequences are then compared to those derived from the PDB file and matched against sequences retrieved from the IPD-IMGT/HLA database for human sequences, or the IPD-MHC database for other species. Mouse sequences are matched against FASTA files from Uniprot. Sequences for the mature extracellular protein (signal petide and cytoplasmic tail removed) are compared to identical length sequences from the datasources mentioned before using either exact matching or Levenshtein distance based matching.


Downloadable data

Data can be downloaded to your local machine from the links below.
Clicking on the clipboard icon will copy the url for the data to your clipboard.
This can then be used to load the structure/data directly from the url into an application like PyMol (for 3D structures) using the load command:
   e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif
or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.
Please take note of the data license. Using data from this site assumes that you have read and will comply with the license.

Complete structures

Aligned structures [cif]
  1. 4HX1 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 4HX1 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 4HX1 assembly 1  
Peptide only [cif]
  1. 4HX1 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/4hx1

Data license

The data above is made available under a Creative Commons CC-BY 4.0 license. This means you can copy, remix, transform, build upon and redistribute the material, but you must give appropriate credit, provide a link to the license, and indicate if changes were made.
If you use any data downloaded from this site in a publication, please cite 'https://www.histo.fyi/'. A preprint is in preparation.

Footnotes